(P 191) SARC024 COHORT D: PHASE 2 TRIAL OF REGORAFENIB IN CHILDREN, ADOLESCENTS, AND ADULTS WITH RHABDOMYOSARCOMA

Objective: Regorafenib is a multi-tyrosine kinase inhibitor that has shown clinical efficacy in several cancer types including some sarcomas like gastrointestinal stromal tumors, osteosarcoma and certain non-adipocytic soft tissue sarcomas. SARC024 is a blanket protocol to study oral regorafenib in patients (pts) with selected sarcoma subtypes. The primary objective of cohort D was to estimate the RECIST 1.1 progression free survival (PFS) rate in pts with rhabdomyosarcoma (RMS) at 8 and 16 weeks (wks). The secondary objectives were to estimate the RECIST 1.1 objective response rate (ORR) at 8 and 16 wks as well as describe the incidence of adverse events secondary to regorafenib.

Methods: Pts ≥5 years (yrs) of age and with the ability to swallow pills, diagnosed with relapsed or refractory embryonal RMS (ERMS) or alveolar RMS (ARMS) with measurable disease according to RECIST 1.1 and had received at least one prior line of systemic chemotherapy, and had recovered from acute toxicities of previous anti-cancer therapies, and with adequate organ function and performance status were included after giving written informed consent. Pts with active CNS disease, severe or uncontrolled medical disease including hypertension, active heart disease, bleeding, thrombosis, seizures, interstitial lung disease, and malabsorption were excluded, as were pregnant or breast-feeding women and those with history of prior treatment with small molecule oral tyrosine kinase inhibitors. Regorafenib was administered once daily orally in 4-week cycles at a dose of 160 mg (82 mg/m2/dose for pts < 18 years of age rounded to the nearest 20 mg) for 3 wks on and 1 wk off and could continue indefinitely until disease progression or physician/pt decision to stop treatment. ORR was measured at 8 wks and 16 wks according to RECIST 1.1 and PFS as time to progression (TTP) from enrollment. Disease control of 30% at 8 wks and ORR of 30% at 8 weeks in a sample size of up to 12 pts was required to consider regorafenib efficacious. Toxicity was assessed according to NCI CTCAE v.4.03.

Results: Ten eligible pts were enrolled between 21Mar2018 and 7Sep2021 at 5 different institutions; 5 were male and 5 were female; median age was 26 yrs (range 16, 63). Eight had metastatic disease There was one grade (gr) 5 pleural effusion secondary to disease progression. There were no unexpected toxicities with single episodes of gr 3 increased ALT, anemia, hypophosphatemia, maculopapular rash, vomiting and single episodes of gr 4 decreased neutrophils, decreased WBC and decreased platelets observed. Nine of 10 patients were evaluable for response and 3 had a best response of stable disease while the remaining 6 had progressive disease. The PFS at 8 wks was 50% (95% CI 26.9-92.9%) and declined to 20% (95%l CI 5.8-69%) at 16 wks.

Conclusion: Regorafenib as a single agent has limited activity in relapsed/refractory RMS. There were no objective responses observed in pts with either ERMS or ARMS enrolled in cohort D of SARC024. PFS exceeded the bar for efficacy set by the trial at 8 weeks but was not sustained at 16 weeks. The EpSSG FAR-RMS trial is investigating the combination of oral regorafenib together with intravenous vincristine and irinotecan in pts with relapsed/refractory RMS (NCT04625907).